A broad long-term research plan in organic sulfur chemistry is outlined that has two aspects. The first aspect is fundamental chemistry. Among many classes of sulfur compounds to be studied, those emphasized will be thiols, disulfides, thiazolidines, sulfenyl derivatives, and sulfinates. Within a framework of uncovering novel principles, as well as details, new syntheses, reactions, structures, and subclasses will be sought. The second aspect is biomedical and involves extensive collaboration with appropriate experts. The chemical and biomedical aspects will be combined and focused in five areas. In approximate priority, these areas are: (1) The arthritides, (a) Penicillamine is now recognized as an important treatment for severe rheumatoid arthritis, but there may be serious side effects. Congeners and latentiated forms will be synthesized to determine optimal features of skeleton, functional group, and latentiation, so that the best features of each can be used in designing more active and/or less toxic variants. New immunochemical and other parameters for evaluating optimal features will be sought, and search for the mechanism(s) of action will be continued. Ancillary applications are anticipated of the compounds in collagen biochemistry and muscular dystrophy. (b) In perhaps related work, blocking agents ("ZOG's"; from zelloberflachengifte) will be sought for SH moieties of lymphocytes. (c) Limited effort is planned on antiinflammatory drugs. (2) The chemistry of disulfides will be explored, with emphasis upon agents (especially ylides) that will insert moieties between the sulfur atoms, upon oxidation, and upon synthesis of thiolsulfonates. (3) Esr spin labels containing sulfur will be sought that will increase the power of esr for studying biochemically important systems. (4) Sulfenyl iodides will be studied in terms of stability, of reactions with phenols and with functions that might serve as traps biochemically, and of function as species that may mediate iodination in the thyroid gland. (5) Drugs will be synthesized for histoplasmosis, primarily with recently developed substituent constants as a guide.